The use of single-use systems has been getting more popular in biologics manufacturing. Utilization of this novel technology enables the efficient manufacturing, including prevention of cross contamination, flexibility to manufacture multiple products, and elimination of the need for cleaning and steam sterilization including those validations. In order to ensure the quality and stable supply of biologics, appropriate risk management considering the characteristics of the system is necessary. However, there is no regulatory document describing the examples or recommendations on it. In 2015, we published the White paper of “Approaches to Quality Risk Management When Using Single-Use Systems in the Manufacture of Biologics” in AAPS PharmSciTech, which was a fruit of discussion in the research group consisting of Japanese pharmaceutical manufacturers, single-use suppliers, academia and regulatory agencies. This review introduces the contents of the White paper with some revision reflecting the comments on it as well as the discussion in our research group after publishing the paper. The basic concept is consistent with ICH guideline on quality risk management. Here we describe the points to consider in risk assessment as well as in risk control when single-use systems are used in biologics manufacturing.

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 抗体医薬品の皮下注開発では，皮下投与可能な薬液量（1 mL程度）を実現させるために高濃度の抗体薬液で安定な処方を見出し，かつ高濃度/高粘性の抗体薬液で安定的に生産できる製法を確立する必要がある。また，慢性疾患では患者さんのQOL向上を目指し，シリンジやオートインジェクターでの皮下注製剤が期待される。これらを踏まえ，本報ではアクテムラ^®皮下注162 mgシリンジ/オートインジェクターの製剤開発における課題への取り組みを紹介する。
 なお，本内容は，日本PDA製薬学会Prefilled Syringe Seminar 2016 Tokyo（2016年5月17, 18日開催）での講演内容に，処方設計及び製法設計の検討情報を追加したものである。

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 Chronic diseases management lead to very specific and challenging set of requirements for the prefillable syringe (PFS) used. Glass PFS based solutions still remains the gold standard that offers a large range of options for injectable biopharmaceuticals.
 A complete overhaul and redesign of the Glass PFS manufacturing process, through a quality by design approach and the introduction of innovative and best in class technologies (have increased significantly the syringe performances until the level required to meet the best in class product specifications with BD Neopak^TM
 BD Neopak Xsi^TM coating, as an inert & immobilized cross-linked silicone for an optimized interfacial contact with biologics, has been developed to maximize the compatibility of the container with the drug product and increase the performance of BD Neopak^TM by eliminating the contribution of the container to the Subvisible particles.
 BD Neopak DuraShield^TM, results from a specific treatment in a molten bath of neat potassium nitrate (KNO₃ molten salt), that enables ions exchange at an atomic level putting the glass under compression. Such treatment increases significantly the BD Neopak^TM breakage resistance and durability (that presents already high level of performance for these criteria) opening the way to overcoming none controlled challenging situations, but at a much higher acquisition cost.

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 Aseptic processing or manufacturing is a method of manufacture in which microorganisms are excluded from the production environment and thereby prevented from entering the product. It has been recognized for decades and humans working in aseptic environments were the only significant source of contamination and therefore posed the greatest risk to both successful production of heat labile products and to the patient. Over the last two decades, there has been a technological evolution in aseptic processing which has greatly increased patient safety by dramatically reducing the risk of microbial contamination in aseptic processing. The improvements that have occurred in aseptic processing arise from two principal technological features. The first of these is the use of isolator technology and the second is the introduction of effective machine automation and robotics. Isolators have reduced contamination risk by effectively separating the human technician from the aseptic environment. Because isolators are an unmanned environment, which is much smaller in volume than a conventional manned clean room, they can be decontaminated in a manner that effectively eliminates microbial contamination of all kinds. The isolator after sporicidal decontamination is effectively a microorganism free environment. The capabilities of the isolator have been further enhanced by the application of robots and other forms of automation. An important recent innovation is the introduction of robotics that could be built into isolator systems and decontaminated in place. These specialized robots along with machine automation have further reduced contamination risk and at the same time eliminated the possibility of technician error. The modern isolator system is very well suited to meeting the cell culture requirements necessary for the production of cytotherapeutics, and as a result cell culture isolators are proving to be the best option for the production of many regenerative medicine products.

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